CN112386646B - Pharmaceutical composition and preparation method and application thereof - Google Patents

Pharmaceutical composition and preparation method and application thereof Download PDF

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CN112386646B
CN112386646B CN201910745363.0A CN201910745363A CN112386646B CN 112386646 B CN112386646 B CN 112386646B CN 201910745363 A CN201910745363 A CN 201910745363A CN 112386646 B CN112386646 B CN 112386646B
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parts
water
substance
essence
clarifying agent
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CN112386646A (en
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曹龙祥
田刚
李超
吴菲
侯学谦
蔡虎
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Jumpcan Pharmaceutical Group Co ltd
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Jumpcan Pharmaceutical Group Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A61K36/634—Forsythia
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/233—Bupleurum
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/484—Glycyrrhiza (licorice)
    • A—HUMAN NECESSITIES
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    • A61K36/18—Magnoliophyta (angiosperms)
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    • A61K36/534—Mentha (mint)
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    • A61K36/18—Magnoliophyta (angiosperms)
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    • A61K36/74—Rubiaceae (Madder family)
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    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/888—Araceae (Arum family), e.g. caladium, calla lily or skunk cabbage
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    • A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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Abstract

The invention relates to the technical field of traditional Chinese medicines, and particularly relates to a pharmaceutical composition, a preparation method and an application thereof, wherein the pharmaceutical composition comprises the following components in parts by weight: 80-90 parts of fructus forsythiae, 60-70 parts of fermented soybean, 40-50 parts of mint, 40-50 parts of schizonepeta, 30-40 parts of fried gardenia, 30-40 parts of rheum officinale, 60-70 parts of sweet wormwood, 40-50 parts of red paeony root, 30-40 parts of betel nut, 60-70 parts of mangnolia officinalis, 60-70 parts of scutellaria baicalensis, 60-70 parts of pinellia ternate, 40-50 parts of radix bupleuri, 30-40 parts of liquorice, 1-5 parts of preservative, 1-5 parts of sweetening agent and 1-5 parts of essence.

Description

Pharmaceutical composition and preparation method and application thereof
Technical Field
The invention relates to the technical field of traditional Chinese medicines, and particularly relates to a pharmaceutical composition, and a preparation method and application thereof.
Background
Common cold is a common exogenous disease, and is often caused by the attack of exogenous pathogenic factors. Clinically, it is mainly characterized by fever, nasal obstruction, nasal discharge, sneezing and cough. The cold is a common disease and a frequently encountered disease in clinic and is also a main disease threatening the health of human beings. Etiology proves that more than 90% of cold is virus infection, and the treatment effect is not ideal by using western medicines such as antibiotics, so that the application of the traditional Chinese medicine to treat influenza is the current research direction. The disease can occur all the year round, often occurs in sudden climate change and in winter and spring, and is the most common disease in pediatrics. The traditional Chinese medicine considers that the cold is caused by wind cold, wind heat and summer-heat dampness, and the phlegm, the clamping stagnation, the convulsion and other accompanied symptoms easily appear after the cold is infected due to the delicate lung, frequent insufficiency of spleen, weak spirit and weak qi of the children. At the beginning of cold, pungent-cool exterior-releasing agents are mostly adopted, but the cold aggravates to the point that exterior pathogens exist outside and interior heat exists inside, muscle-releasing and fever-abating traditional Chinese medicines are usually needed to be given, but the traditional Chinese patent medicines are quite lacking at present. Especially, the clinical application of the medicament for children is less.
Wind-heat type common cold in children is manifested by severe fever, mild aversion to cold, aversion to wind, sweating or hypohidrosis, headache, nasal obstruction, thick nasal discharge, sneezing, cough, thick sputum, white or yellow color, red swelling and pain of pharynx, thirst, red tongue, yellow tongue coating, and superficial and rapid pulse or superficial and purple finger print; the clinical symptoms of fever, sweating, headache, nasal obstruction, thirst, throat swelling and pain, red tongue and yellow tongue coating can also appear after the patients feel summer-heat and dampness or the pathogens of epidemic; the "Wen Bing Bian Yan Lun" mentioned the treatment of cold plague: for either four seasons or some syndromes, it is used with pungent-warm property to relieve muscular fatigue when it does not transform heat and has aversion to cold; after the heat is dissolved, if the patient is warm, the heat is cleared away with pungent and cool herbs, and there is no reason for the two. Although cold epidemic invasion is involved, it is also accompanied by wind-heat syndrome after yang transformation into heat. The exogenous febrile disease of children accounts for about 80% of exogenous diseases.
In recent years, with the increasingly worsened environment, children have low immunity and cannot resist the invasion of various microorganisms and viruses in the environment, but many children have large emotional conflict on traditional Chinese medicines and Chinese patent medicines, the compliance of the traditional Chinese medicines is low, the traditional Chinese medicine components are complex, the quality standard is not clear, and consumers cannot use the traditional Chinese medicines with confidence.
Patent application CN1733182A discloses a pharmaceutical composition for treating exogenous fever, which is basically prepared from fructus forsythiae, fermented soybean, mint, herba schizonepetae, fructus gardeniae, rhubarb, sweet wormwood, red paeony root, areca nut, mangnolia officinalis, radix scutellariae, pinellia ternate, radix bupleuri and liquorice, and can be prepared into granules, capsules, oral liquid and tablets. The patent improves the taste of the pharmaceutical composition to a certain extent, but the types and contents of the active ingredients in the composition are further determined and improved.
Patent application CN 109223930A discloses a medicinal syrup for treating wind-heat type common cold in children and a preparation method thereof, wherein each mL of the syrup comprises 0.0024-0.02mg of beta-pinene, 0.0050-0.2mg of menthol, 0.068-3mg of forsythin and 0.64-5mg of geniposide. The raw materials comprise 80-90 parts of fructus forsythiae, 60-70 parts of fermented soybean, 40-50 parts of mint, 40-50 parts of herba schizonepetae, 30-40 parts of fructus gardeniae, 30-40 parts of rheum officinale, 60-70 parts of sweet wormwood herb, 40-50 parts of red paeony root, 28-35 parts of betel nut, 60-70 parts of mangnolia officinalis, 60-70 parts of radix scutellariae, 60-70 parts of pinellia ternate, 40-50 parts of radix bupleuri and 30-40 parts of liquorice. The patent improves the compliance of the children patients to take to a certain extent, but the effective components in the syrup need to be improved, the inclusion effect of the volatile oil needs to be improved, and further, the compliance of the children patients to take needs to be further improved.
For another example, the common antipyretic in the market is Xiao' er jin Dan which is prepared from cinnabar, red tangerine peel, tendril-leaved fritillary bulb, arisaema cum bile, whiteflower hogfennel root, figwort and other medicines, but cinnabar contains a large amount of metallic mercury, has great toxic and side effects on the body and has great influence on the growth and development of children in particular. Shuanghuanglian oral liquid is also a commonly used medicine for treating wind-heat type common cold, but the taste is bitter, and most children patients refuse to take the oral liquid. Therefore, it is necessary to provide a drug having a definite drug action and high compliance for children patients.
Therefore, it is necessary to develop a pharmaceutical composition and a method for preparing the same, which can solve the above-mentioned problems.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a pharmaceutical composition with high content of effective components, high stability and good compliance for children patients to take, and a preparation method and application thereof.
The invention is realized by the following technical scheme:
a pharmaceutical composition comprises the following components in parts by weight: 80-90 parts of fructus forsythiae, 60-70 parts of fermented soybean, 40-50 parts of mint, 40-50 parts of schizonepeta, 30-40 parts of fried gardenia, 30-40 parts of rheum officinale, 60-70 parts of sweet wormwood, 40-50 parts of red paeony root, 30-40 parts of betel nut, 60-70 parts of mangnolia officinalis, 60-70 parts of scutellaria baicalensis, 60-70 parts of pinellia ternate, 40-50 parts of radix bupleuri, 30-40 parts of liquorice, 1-5 parts of preservative, 1-5 parts of sweetener and 1-5 parts of essence.
Preferably, the pharmaceutical composition comprises the following components in parts by weight: 85-90 parts of fructus forsythiae, 65-68 parts of fermented soybean, 42-46 parts of mint, 43-46 parts of schizonepeta, 35-40 parts of fried gardenia, 36-39 parts of rheum officinale, 65-70 parts of sweet wormwood, 42-46 parts of red paeony root, 30-35 parts of betel nut, 64-68 parts of mangnolia officinalis, 64-68 parts of scutellaria baicalensis, 64-68 parts of pinellia ternate, 42-46 parts of radix bupleuri, 35-39 parts of liquorice, 2-4 parts of preservative, 2-4 parts of sweetener and 2-4 parts of essence.
Preferably, the sweetener is one or more of sucrose, high fructose syrup, xylitol, glycyrrhizin, and steviol glycosides.
More preferably, the sweetener is one or both of a steviol glycoside and a high fructose syrup.
Preferably, the preservative is one or more of potassium sorbate, benzoic acid, hydroxybenzyl ester, ethylparaben, propylparaben, and butylparaben.
More preferably, the preservative is one or both of potassium sorbate and hydroxypropyl paraben.
More preferably, the preservative is a mixture of potassium sorbate and hydroxypropyl hydroxybenzoate in a mass ratio of 0.5-2: 1.
Preferably, the essence is one or more of orange essence, strawberry essence, lemon essence, blueberry essence, raspberry essence, blackberry essence, waxberry essence, smoked plum essence and preserved plum essence.
More preferably, the essence is orange essence.
The invention also relates to an infantile heat-clearing oral liquid containing fermented soya beans and fructus forsythiae, which comprises the pharmaceutical composition.
Preferably, the children heat-clearing oral liquid prepared from fermented soybeans and fructus forsythiae further comprises pharmaceutically acceptable auxiliary materials.
More preferably, the pharmaceutically acceptable excipient comprises dextrin.
Preferably, the dextrin is one or two of hydroxypropyl-beta-cyclodextrin and sulfobutyl-beta-cyclodextrin.
More preferably, the dextrin is sulfobutyl- β -cyclodextrin.
The invention also relates to a preparation method of the children fermented soybean and fructus forsythiae heat-clearing oral liquid, which comprises the following steps:
(1) decocting fructus forsythiae, herba Menthae, herba Schizonepetae, and bupleuri radix with water, distilling to extract volatile oil, mixing with organic solvent I to obtain substance A, and collecting the water solution and the residue after volatile oil extraction;
(2) adding dextrin into water, stirring, and adding the substance A to obtain a substance B;
(3) decocting semen Sojae Preparatum, fructus Gardeniae preparata, radix et rhizoma Rhei, herba Artemisiae Annuae, radix Paeoniae Rubra, Arecae semen, cortex Magnolia officinalis, Scutellariae radix, rhizoma Pinelliae, Glycyrrhrizae radix and the residue in step (1) with water for 1-3 times, filtering, mixing the decoctions and the distilled water solution in step (1) to obtain solution C;
(4) concentrating the solution C, mixing with an organic solvent II, standing, filtering, recovering the organic solvent II in the filtrate, and concentrating to obtain a substance D;
(5) mixing the substance D and the substance B, adding water, filtering, mixing the filtrate with sweetener, antiseptic and essence, adding clarifier, standing, and filtering to obtain filtrate E;
(6) and sterilizing the filtrate E to obtain the compound.
Preferably, in the step (1), the mass ratio of the total mass of the forsythia, the mint, the schizonepeta and the radix bupleuri to water is 1:4-6, water is added for decoction for 2-4h, the organic solvent I is 40-80% of ethanol, and the volume ratio of the volatile oil to the ethanol is 1: 0.8-1.2.
More preferably, the organic solvent I is 50-70% ethanol.
Preferably, in the step (2), dextrin is added into water with the temperature of 85-95 ℃ to prepare a dextrin water solution with the mass fraction of 55-65%, the dextrin water solution is cooled to 40-50 ℃, and ultrasonic treatment is carried out while the dextrin water solution is stirred, and the substance A is added to obtain the substance B.
Preferably, the mass-volume ratio of the dextrin to the volatile oil in the step (1) is 14-18:1 g/mL.
More preferably, the mass-to-volume ratio of the dextrin to the volatile oil in the step (1) is 16:1 g/mL.
More preferably, in the step (2), ultrasonic treatment is carried out for 5-10min while dextrin aqueous solution is stirred, 50-60% of the substance A is added, after the addition is finished, ultrasonic treatment is carried out for 30-60min, colloidal silicon dioxide SYLOID244FP is added, grinding is carried out, the rest substance A is added, grinding and drying are carried out, washing is carried out by absolute ethyl alcohol, and drying is carried out, so as to obtain the substance B.
More preferably, the volume-to-mass ratio of the volatile oil to the colloidal silicon dioxide SYLOID244FP is 1:1-3 mL/g.
More preferably, the colloidal silicon dioxide SYLOID244FP is added in the step (2), the mixture is ground into paste, the grinding is continued at the temperature of 40-50 ℃, the residual substance A is added, the grinding is carried out for 1-2h, the vacuum drying is carried out until the substance is nearly dried, the suction filtration is carried out, the absolute ethyl alcohol is used for washing, and the vacuum drying is carried out at the temperature of 50-70 ℃ to obtain the substance B.
More preferably, the step (2) is as follows: adding dextrin into water at 85-95 ℃ to prepare a dextrin aqueous solution with the mass fraction of 55-65%, cooling to 40-50 ℃, carrying out ultrasonic treatment for 5-10min while stirring the dextrin aqueous solution, adding 50-60% of a substance A, continuing the ultrasonic treatment for 30-60min after the addition is finished, adding colloidal silicon dioxide SYLOID244FP according to the volume mass ratio of 1:1-3mL/g of volatile oil to colloidal silicon dioxide SYLOID244FP, grinding to paste, continuing the grinding at 40-50 ℃, adding the rest substance A, grinding for 1-2h, vacuum drying to near dryness, carrying out suction filtration, washing with absolute ethyl alcohol, and vacuum drying at 50-70 ℃ to obtain a substance B.
Preferably, the fermented soybean, the fried gardenia, the rhubarb, the sweet wormwood herb, the red paeony root, the betel nut, the magnolia officinalis, the scutellaria baicalensis, the pinellia ternate and the liquorice in the step (3) and the dregs in the step (1) are decocted for 2 times by adding water, the 1 st time is decocted for 1-2 hours by adding 7-9 times of water, and the 2 nd time is decocted for 0.5-1.5 hours by adding 5-7 times of water.
Preferably, the organic solvent II in the step (4) is absolute ethyl alcohol.
Preferably, in the step (4), the solution C is concentrated to 55 ℃ and has a relative density of 1.05-1.10, and is mixed with absolute ethyl alcohol to ensure that the alcohol content is 60-70%, the mixture is kept stand for 10-15h, filtered, the ethyl alcohol in the filtrate is recovered, and the solution C is concentrated to 55 ℃ and has a relative density of 1.08-1.12 to obtain the substance D.
Preferably, the filtrate obtained in the step (5) is mixed with a sweetening agent, a preservative and essence, boiled for 0.5-1h, added with a primary clarifying agent, kept stand, filtered, added with a secondary clarifying agent, added with water and filtered to obtain a filtrate E.
More preferably, the primary clarifier is one or more of a 101 fruit juice clarifier, a ZTC1+1 clarifier, a JH clarifier and gelatin.
More preferably, the secondary clarifying agent is one or more of chitosan, ZTC1+1 clarifying agent, JH clarifying agent, gelatin, 101 juice clarifying agent. And the primary fining agent and the secondary fining agent are different fining agents.
More preferably, the primary clarifier is a JH clarifier and the secondary clarifier is chitosan.
More preferably, the filtrate obtained in the step (5) is mixed with a sweetening agent, a preservative and essence, boiled for 0.5-1h, added with a JH clarifying agent, kept stand for 25-40min, filtered, added with chitosan, added with water and filtered to obtain a filtrate E.
More preferably, the mass ratio of the preservative to the JH clarifying agent in the step (5) is 1:8-10, and the mass ratio of the preservative to the chitosan is 1: 4-6.
Preferably, the sterilization mode in the step (6) is ultrahigh static pressure sterilization.
More preferably, the ultra-high static pressure sterilization step is as follows: and (3) placing the filtrate in an ultrahigh static pressure sterilization instrument, and setting the ultrahigh static pressure to be 200-400 MPa and the treatment time to be 20-35 min.
The invention also relates to application of the pharmaceutical composition or the infantile fermented soybean and fructus forsythiae heat-clearing oral liquid prepared by the preparation method in preparation of a medicine for treating infantile wind-heat type common cold.
The invention has the beneficial effects that:
the dextrin selected by the invention is hydroxypropyl-beta-cyclodextrin or sulfobutyl-beta-cyclodextrin, has good water solubility, adopts a liquid-liquid inclusion mode, is favorable for inclusion of volatile oil to obtain a liquid inclusion compound, is favorable for preparation of an oral liquid preparation, and particularly has a remarkably improved inclusion effect when sulfobutyl-beta-cyclodextrin is selected.
When the dextrin inclusion and the ultrasonic colloid milling method are combined for use, the volatile oil is included by the dextrin assisted by the colloidal silicon dioxide, the encapsulation efficiency is higher, the heating temperature in the inclusion process is lower, and the volatile oil components are retained to the maximum extent. The volatile oil of the infantile fermented soybean and fructus forsythiae is the effective component, and the prepared oral liquid can obviously improve the stability and the content of the effective component, thereby ensuring the product quality. In addition, volatile oil can be fully locked after inclusion, the volatile oil on the surface of the inclusion compound is washed away by absolute ethyl alcohol, peculiar smell is locked, and the taste of the oral liquid is improved.
The product of the invention is mainly used for treating wind-heat type common cold of children, and the children patients have higher requirements for the taste of the medicine.
The invention uses two-stage clarifying agents to carry out solid-liquid separation, reduces the early standing time, shortens the production period and ensures that the product quality is more stable. In addition, when the preservative is a mixture of potassium sorbate and hydroxy propyl ester, and the proportion of the two is limited, the stability of the prepared product can be further improved.
The invention adopts the ultrahigh static pressure sterilization method for sterilization, reduces the loss of the content of the active ingredients caused by sterilization, has higher content of the active ingredients of the final product and shorter sterilization time, and shortens the production period.
Detailed Description
The invention will be further described with reference to specific embodiments, and the advantages and features of the invention will become apparent as the description proceeds. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.
Example 1
A pharmaceutical composition comprising the following components: 80g of fructus forsythiae, 60g of fermented soybean, 40g of mint, 40g of herba schizonepetae, 30g of fried gardenia, 30g of rheum officinale, 60g of sweet wormwood, 40g of red paeony root, 30g of betel nut, 60g of mangnolia officinalis, 60g of scutellaria baicalensis, 60g of pinellia ternate, 40g of radix bupleuri, 30g of liquorice, 1g of benzoic acid, 1g of cane sugar and 1g of strawberry essence.
Example 2
A pharmaceutical composition comprising the following components: 90g of fructus forsythiae, 70g of fermented soybean, 50g of mint, 50g of herba schizonepetae, 40g of fried gardenia, 40g of rheum officinale, 70g of sweet wormwood, 50g of red paeony root, 40g of betel nut, 70g of mangnolia officinalis, 70g of scutellaria baicalensis, 70g of pinellia ternate, 50g of radix bupleuri, 40g of liquorice, 5g of ethylparaben, 5g of glycyrrhizin and 5g of lemon essence.
Example 3
A pharmaceutical composition comprising the following components: 85g of fructus forsythiae, 65g of fermented soybean, 42g of mint, 43g of herba schizonepetae, 35g of fried fructus gardeniae, 36g of rheum officinale, 65g of sweet wormwood, 42g of red paeony root, 30g of betel nut, 64g of mangnolia officinalis, 64g of scutellaria baicalensis, 64g of pinellia ternate, 42g of radix bupleuri, 35g of liquorice, 2g of preservative, 2g of high fructose syrup and 2g of blueberry essence, wherein the preservative is a mixture of potassium sorbate and propyl hydroxybenzoate, and the mass ratio of the two is 0.5: 1.
Example 4
A pharmaceutical composition comprising the following components: 88g of fructus forsythiae, 67g of fermented soybean, 44g of mint, 44g of herba schizonepetae, 38g of fried gardenia, 38g of rheum officinale, 66g of sweet wormwood herb, 44g of red paeony root, 34g of betel nut, 67g of mangnolia officinalis, 67g of scutellaria baicalensis, 67g of pinellia ternate, 44g of radix bupleuri, 37g of liquorice, 2g of preservative, 2g of stevioside and 2g of orange essence, wherein the preservative is a mixture of potassium sorbate and propyl hydroxybenzoate, and the mass ratio of the two is 2: 1.
Example 5
A pharmaceutical composition comprising the following components: 88g of fructus forsythiae, 67g of fermented soybean, 44g of mint, 44g of herba schizonepetae, 38g of fried gardenia, 38g of rheum officinale, 66g of sweet wormwood herb, 44g of red paeony root, 34g of betel nut, 67g of mangnolia officinalis, 67g of scutellaria baicalensis, 67g of pinellia ternate, 44g of radix bupleuri, 37g of liquorice, 2g of preservative, 2g of stevioside and 2g of orange essence, wherein the preservative is a mixture of potassium sorbate and propyl hydroxybenzoate, and the mass ratio of the two is 1:1.
Example 6
An oral liquid for clearing heat from children, prepared from the pharmaceutical composition of example 2 and hydroxypropyl-beta-cyclodextrin, comprises the following steps:
(1) decocting fructus forsythiae, herba Menthae, herba Schizonepetae, and bupleuri radix with 4 times of water for 2 hr, distilling to extract volatile oil, mixing volatile oil with 40% ethanol at a volume ratio of 1:0.8 to obtain substance A, and collecting the water solution and the residue after volatile oil extraction;
(2) adding hydroxypropyl-beta-cyclodextrin into water at 85 ℃ to prepare a hydroxypropyl-beta-cyclodextrin aqueous solution with the mass fraction of 55%, wherein the mass volume ratio of the dextrin to the volatile oil in the step (1) is 14:1g/mL, cooling to 40 ℃, carrying out ultrasonic treatment for 5min while stirring the hydroxypropyl-beta-cyclodextrin aqueous solution, and adding a substance A to obtain a substance B;
(3) decocting fermented soybean, fried gardenia, rhubarb, sweet wormwood, red paeony root, areca nut, mangnolia officinalis, scutellaria baicalensis, pinellia ternate and liquorice with 7 times of water for 3 hours, filtering, and combining decoction and the distilled water solution obtained in the step (1) to obtain a solution C;
(4) concentrating the solution C to 55 deg.C relative density of 1.05, mixing with anhydrous ethanol to make ethanol content 60%, standing for 10 hr, filtering, recovering ethanol from filtrate, and concentrating to 55 deg.C relative density of 1.08 to obtain substance D;
(5) mixing the substance D and the substance B, adding water to 800mL, filtering, mixing the filtrate with ethylparaben, glycyrrhizin and lemon essence, boiling for 0.5h, adding 40g of ZTC1+1 clarifier, standing for 40min, filtering, adding 20g of JH clarifier into the filtrate, adding water to 1000mL, and filtering to obtain filtrate E;
(6) and (3) placing the filtrate E in an ultrahigh static pressure sterilization instrument, and setting the ultrahigh static pressure to be 200MPa, wherein the treatment time is 20 min.
Example 7
The difference from example 6 is only that the preparation method is different from step (2), and the rest conditions are the same, specifically as follows:
(2) adding hydroxypropyl-beta-cyclodextrin into water at 85 ℃ to prepare hydroxypropyl-beta-cyclodextrin water solution with the mass fraction of 55%, wherein the mass volume ratio of dextrin to the volatile oil in the step (1) is 14:1g/mL, cooling to 40 ℃, carrying out ultrasonic treatment for 5min while stirring the hydroxypropyl-beta-cyclodextrin water solution, adding 50% of substance A, continuing ultrasonic treatment for 30min after the addition is finished, adding colloidal silicon dioxide SYLOID244FP according to the volume ratio of the volatile oil to the colloidal silicon dioxide SYLOID244FP of 1:1mL/g, stirring and grinding while adding, grinding to paste, continuing grinding at 40 ℃, adding the rest substance A, grinding for 1h, vacuum drying to near dry, carrying out suction filtration, washing with absolute ethyl alcohol, and vacuum drying at 50 ℃ to obtain substance B.
Example 8
An oral liquid for clearing heat from children, prepared from the pharmaceutical composition of example 3 and sulfobutyl-beta-cyclodextrin, comprises the following steps:
(1) decocting fructus forsythiae, herba Menthae, herba Schizonepetae, and bupleuri radix with 6 times of water for 4 hr, distilling to extract volatile oil, mixing volatile oil with 80% ethanol at a volume ratio of 1:1.2 to obtain substance A, and collecting the water solution and the residue after volatile oil extraction;
(2) adding sulfobutyl-beta-cyclodextrin into 95 ℃ water to prepare 65% sulfobutyl-beta-cyclodextrin aqueous solution, wherein the mass volume ratio of dextrin to the volatile oil in the step (1) is 18:1g/mL, cooling to 50 ℃, carrying out ultrasonic treatment for 10min while stirring the sulfobutyl-beta-cyclodextrin aqueous solution, adding 60% of a substance A, continuing to carry out ultrasonic treatment for 60min after the addition is finished, adding colloidal silicon dioxide SYLOID244FP according to the volume mass ratio of the volatile oil to the colloidal silicon dioxide SYLOID244FP of 1:3mL/g, stirring and grinding while adding, grinding to paste, continuing to grind at 50 ℃, adding the rest substance A, grinding for 2h, carrying out vacuum drying to near dryness, carrying out suction filtration, washing with absolute ethyl alcohol, and carrying out vacuum drying at 70 ℃ to obtain a substance B;
(3) decocting semen Sojae Preparatum, fructus Gardeniae preparata, radix et rhizoma Rhei, herba Artemisiae Annuae, radix Paeoniae Rubra, Arecae semen, cortex Magnolia officinalis, Scutellariae radix, rhizoma Pinelliae, Glycyrrhrizae radix and the residue in step (1) with 9 times of water for 1.5h, filtering, decocting repeatedly for 3 times, mixing the decoctions and the distilled water solution in step (1) to obtain solution C;
(4) concentrating the solution C to 55 deg.C relative density of 1.10, mixing with anhydrous ethanol to make ethanol content 70%, standing for 15 hr, filtering, recovering ethanol from filtrate, and concentrating to 55 deg.C relative density of 1.12 to obtain substance D;
(5) mixing the substance D and the substance B, adding water to 800mL, filtering, mixing the filtrate with antiseptic, high fructose syrup and blueberry essence, boiling for 1h, adding 20g 101 of fruit juice clarifier, standing for 25min, filtering, adding 12g of gelatin into the filtrate, adding water to 1000mL, and filtering to obtain filtrate E;
(6) and (3) placing the filtrate E in an ultrahigh static pressure sterilization instrument, setting the ultrahigh static pressure to be 400MPa, and treating for 35min to obtain the filtrate E.
Example 9
The difference from example 8 is only that the preparation is carried out using the pharmaceutical composition of example 3 and hydroxypropyl-beta-cyclodextrin, and the other conditions are the same.
Example 10
An oral liquid for clearing heat from children, prepared from the pharmaceutical composition of example 4 and sulfobutyl-beta-cyclodextrin, comprises the following steps:
(1) decocting fructus forsythiae, herba Menthae, herba Schizonepetae, and bupleuri radix with 5 times of water for 3 hr, distilling to extract volatile oil, mixing volatile oil with 60% ethanol at a volume ratio of 1:1 to obtain substance A, and collecting the water solution and the residue after volatile oil extraction;
(2) adding sulfobutyl-beta-cyclodextrin into water at 90 ℃ to prepare sulfobutyl-beta-cyclodextrin aqueous solution with the mass fraction of 60%, wherein the mass volume ratio of the dextrin to the volatile oil in the step (1) is 16:1g/mL, cooling to 45 ℃, carrying out ultrasonic treatment for 8min while stirring the sulfobutyl-beta-cyclodextrin aqueous solution, adding 55% of a substance A, continuing to carry out ultrasonic treatment for 45min after the addition is finished, adding colloidal silicon dioxide SYLOID244FP according to the volume mass ratio of the volatile oil to the colloidal silicon dioxide SYLOID244FP of 1:2mL/g, stirring and grinding while adding to be pasty, continuing to grind at 45 ℃, adding the rest substance A, grinding for 1.5h, vacuum drying to be nearly dry, carrying out suction filtration, washing with absolute ethyl alcohol, and carrying out vacuum drying at 60 ℃ to obtain a substance B;
(3) decocting the fermented soybean, the fried gardenia, the rhubarb, the sweet wormwood herb, the red paeony root, the areca nut, the mangnolia officinalis, the scutellaria baicalensis, the pinellia ternate and the liquorice with the dregs obtained in the step (1) in water for 2 times, adding 7 times of water for 1 hour for the 1 st time, adding 5 times of water for 0.5 hour for the 2 nd time, filtering, and combining decoction and the distilled water solution obtained in the step (1) to obtain a solution C;
(4) concentrating the solution C to 55 deg.C relative density of 1.08, mixing with anhydrous ethanol to make ethanol content 65%, standing for 12 hr, filtering, recovering ethanol from filtrate, and concentrating to 55 deg.C relative density of 1.10 to obtain substance D;
(5) mixing the substance D and the substance B, adding water to 800mL, filtering, mixing the filtrate with a preservative, stevioside and orange essence, boiling for 0.75h, adding 36g of JH clarifier, standing for 30min, filtering, adding 20g of chitosan into the filtrate, adding water to 1000mL, and filtering to obtain a filtrate E;
(6) and (3) placing the filtrate E in an ultrahigh static pressure sterilization instrument, setting the ultrahigh static pressure to be 300MPa, and treating for 25min to obtain the product.
Example 11
A pharmaceutical composition comprising the following components: 88g of fructus forsythiae, 67g of fermented soybean, 44g of mint, 44g of herba schizonepetae, 38g of fried gardenia, 38g of rheum officinale, 66g of sweet wormwood herb, 44g of red paeony root, 34g of betel nut, 67g of mangnolia officinalis, 67g of scutellaria baicalensis, 67g of pinellia ternate, 44g of radix bupleuri, 37g of liquorice, 2g of potassium sorbate, 2g of stevioside and 2g of orange essence.
Example 12
An oral liquid, which is prepared from fermented soybean and fructus forsythiae for clearing heat for children, differs from the oral liquid in example 10 only in that the pharmaceutical composition in example 11 and sulfobutyl-beta-cyclodextrin are used for preparation, and the other conditions are the same.
Example 13
An oral liquid, which is prepared from fermented soybean and fructus forsythiae for clearing heat for children, differs from the oral liquid in example 10 only in that the pharmaceutical composition in example 5 and sulfobutyl-beta-cyclodextrin are used for preparation, and the other conditions are the same.
Example 14
An oral liquid, which is prepared from fermented soybean and fructus forsythiae for clearing heat for children, is different from the oral liquid in example 10 only in that the pharmaceutical composition in example 1 and sulfobutyl-beta-cyclodextrin are used for preparation, and the other conditions are the same.
Comparative example 1
The only difference compared to example 13 is that the dextrin was beta-cyclodextrin, and the other conditions were the same.
Comparative example 2
Compared with the embodiment 13, the difference is that the step (5) adopts vacuum filtration without adding a clarifying agent, and the rest conditions are the same as follows:
mixing the substance D and the substance B, adding water to 800mL, filtering, mixing the filtrate with potassium sorbate, stevioside and orange essence, boiling for 0.75h, standing for 60min, vacuum-filtering, adding water to 1000mL, and vacuum-filtering to obtain a filtrate E;
comparative example 3
Compared with the example 13, the difference is that the sterilization method in the step (6) is high-temperature and high-pressure sterilization, and the rest conditions are the same, which are as follows:
(6) placing the filtrate E in a high-pressure steam sterilizer, setting the temperature at 105 ℃, and sterilizing for 30 minutes to obtain the product.
Comparative example 4
Compared with the example 13, the only difference is that the primary clarifying agent in the step (5) is tannin, the secondary clarifying agent is sodium alginate, and the rest conditions are the same.
Test example 1
Examples 6-9, example 13 and comparative example 1 were subjected to inclusion rate test
Precisely weighing a certain amount of the inclusion compound (namely the substance B), operating according to the volatile oil determination item in appendix XD in the first part of the version 2010 of Chinese pharmacopoeia, and reading the volume of the volatile oil in the inclusion compound.
Precisely measuring 1.0mL of volatile oil, operating according to the volatile oil determination item in appendix XD of first part of Chinese pharmacopoeia 2010 edition, reading the volume of the volatile oil, and calculating the blank recovery (%).
Calculating the inclusion rate of the volatile oil according to the following formula:
Figure BDA0002165380460000091
the results are shown in Table 1. The higher the inclusion rate, the better the inclusion effect.
TABLE 1 Inclusion Rate test results
Inclusion rate/%)
Example 6 65
Example 7 78
Example 8 85
Example 9 80
Example 13 89
Comparative example 1 56
Test example 2
Examples 6, 8, 10, 12, 13 and comparative examples 2 to 4 were subjected to stability test
After the preparation of the finished product, the properties of the oral liquid were observed after 0 month, 3 months, 6 months, 12 months and 18 months, respectively, and whether or not precipitation occurred was observed, and the results are shown in table 2. Precipitation appeared, indicating poor stability.
Table 2 product stability testing
Figure BDA0002165380460000101
The heat-clearing oral liquid prepared in examples 10, 12 and 13 is used as a sample to investigate the bacteriostatic effect of the preservative. The specific operation steps are as follows:
respectively taking 5mL of samples of examples 10, 12 and 13, placing the samples in a U-shaped tube, adding yeast with two parts per million by mass into each sample, simultaneously placing the three samples in the same constant temperature and humidity box for culturing for 24 hours at the temperature of 37-40 ℃ and the humidity of 45-60% RH, observing whether gas is produced, and repeating the experiment for two times for the three samples. By observing that the sample of example 10 has a small amount of bubbles, the sample of example 12 has a large amount of bubbles, the sample of example 13 has no bubbles, and the bacteriostatic effects of the three examples are example 13 > example 10 > example 12.
Test example 3
Examples 6 to 10, examples 12 to 13 and comparative examples 1 to 4 were tested for the content of active ingredient, and the oral liquid before sterilization was used as a control (i.e., filtrate E of example 13 was examined).
The content of the active ingredients of phillyrin and geniposide is determined by the following test method:
geniposide detection
Chromatographic condition and system adaptability test: octadecylsilane chemically bonded silica is used as a filling agent; acetonitrile-water (9:91) is used as a mobile phase; the column temperature is 30 ℃; the detection wavelength was 238 nm. The number of theoretical plates is not less than 3000 calculated according to geniposide peak.
Preparation of control solutions: taking appropriate amount of geniposide reference substance, precisely weighing, and dissolving with mobile phase to obtain solution containing 20 μ g per 1 mL.
Preparation of a test solution: precisely measuring 1mL of the oral liquid, placing in a 20mL measuring flask, adding methanol to scale, sealing, ultrasonically treating for 30min, cooling, shaking, and filtering. Precisely measuring 1mL of the subsequent filtrate, placing in a 5mL measuring flask, adding mobile phase to dilute to scale, and shaking up to obtain the final product.
The determination method comprises the following steps: precisely sucking 20 μ l of each of the reference solution and the sample solution, injecting into liquid chromatograph, and measuring.
Forsythiaside detection
Chromatographic condition and system adaptability test: octadecylsilane chemically bonded silica is used as a filling agent; acetonitrile-water (22:78) is used as a mobile phase; the column temperature is 35 ℃; the detection wavelength was 277 nm. The number of theoretical plates is not less than 3000 calculated according to phillyrin peak.
Preparation of control solutions: taking a proper amount of phillyrin reference substance, precisely weighing, and dissolving with methanol to obtain a solution containing 0.1g of phillyrin per 1 mL.
Preparation of a test solution: precisely measuring 1mL of the oral liquid, placing in a 25mL measuring flask, adding methanol to scale, performing ultrasonic treatment for 30 minutes, cooling, shaking, and filtering. Precisely measuring 10mL of subsequent filtrate, evaporating to dryness, dissolving with 5mL of 70% ethanol, adding onto a neutral alumina column (100 meshes 200, 2g, column inner diameter 1.5cm), eluting with 80mL of 70% ethanol, collecting eluate, concentrating to dryness, dissolving residue with 50% methanol, transferring into a 5mL measuring flask, diluting to scale, shaking, filtering, and collecting subsequent filtrate.
The determination method comprises the following steps: precisely sucking 20 μ l of each of the reference solution and the sample solution, injecting into liquid chromatograph, and measuring.
The test results are shown in table 3.
TABLE 3 determination of the content of active ingredients
Figure BDA0002165380460000111
Figure BDA0002165380460000121
The technical means disclosed by the scheme of the invention are not limited to the technical means disclosed by the technical means, and the technical scheme also comprises the technical scheme formed by any combination of the technical characteristics. While the foregoing is directed to embodiments of the present invention, it will be appreciated by those skilled in the art that various changes may be made in the embodiments without departing from the principles of the invention, and that such changes and modifications are intended to be included within the scope of the invention.

Claims (7)

1. The children fermented soybean and fructus forsythiae heat-clearing oral liquid is characterized by comprising the following components in parts by weight: 80-90 parts of fructus forsythiae, 60-70 parts of fermented soybean, 40-50 parts of mint, 40-50 parts of schizonepeta, 30-40 parts of fried gardenia, 30-40 parts of rheum officinale, 60-70 parts of sweet wormwood, 40-50 parts of red paeony root, 30-40 parts of betel nut, 60-70 parts of mangnolia officinalis, 60-70 parts of scutellaria baicalensis, 60-70 parts of pinellia ternate, 40-50 parts of radix bupleuri, 30-40 parts of liquorice, 1-5 parts of preservative, 1-5 parts of sweetener and 1-5 parts of essence; the preservative is a mixture of potassium sorbate and propyl hydroxybenzoate, and the mass ratio of the potassium sorbate to the propyl hydroxybenzoate is 0.5-2: 1;
the children heat clearing oral liquid with fermented soybean and fructus forsythiae further comprises pharmaceutically acceptable auxiliary materials, wherein the pharmaceutically acceptable auxiliary materials comprise dextrin, and the dextrin is sulfobutyl-beta-cyclodextrin;
the preparation method of the children heat-clearing oral liquid containing fermented soya beans and fructus forsythiae comprises the following steps:
(1) decocting fructus forsythiae, herba Menthae, herba Schizonepetae, and bupleuri radix in water, extracting volatile oil by steam distillation, mixing with 40-80% ethanol to obtain substance A, and collecting the water solution and the residue; in the step (1), the mass ratio of the total mass of the forsythia, the mint, the schizonepeta and the radix bupleuri to water is 1:4-6, the decoction is carried out for 2-4h, and the volume ratio of the volatile oil to 40-80% of ethanol is 1: 0.8-1.2;
(2) adding dextrin into water at 85-95 ℃ to prepare a dextrin water solution with the mass fraction of 55-65%, cooling to 40-50 ℃, carrying out ultrasonic treatment while stirring the dextrin water solution, adding 50-60% of a substance A, continuing ultrasonic treatment for 30-60min after the addition is finished, adding colloidal silicon dioxide SYLOID244FP, grinding, adding the rest substance A, grinding, drying, washing with absolute ethyl alcohol, and drying to obtain a substance B, wherein the mass-volume ratio of the dextrin to the volatile oil in the step (1) is 14-18:1 g/mL;
(3) decocting semen Sojae Preparatum, fructus Gardeniae preparata, radix et rhizoma Rhei, herba Artemisiae Annuae, radix Paeoniae Rubra, Arecae semen, cortex Magnolia officinalis, Scutellariae radix, rhizoma Pinelliae, Glycyrrhrizae radix and the residue in step (1) with water for 1-3 times, filtering, mixing the decoctions and the distilled water solution in step (1) to obtain solution C;
(4) concentrating the solution C to 55 deg.C relative density of 1.05-1.10, mixing with anhydrous ethanol to make ethanol content 60-70%, standing for 10-15 hr, filtering, recovering ethanol from filtrate, and concentrating to 55 deg.C relative density of 1.08-1.12 to obtain substance D;
(5) mixing substance D and substance B, adding water, filtering, mixing the filtrate with sweetener, antiseptic and essence, boiling for 0.5-1 hr, adding primary clarifier, standing, filtering, adding secondary clarifier, adding water, and filtering to obtain filtrate E; the primary clarifying agent is one or more of a 101 fruit juice clarifying agent, a ZTC1+1 clarifying agent, a JH clarifying agent and gelatin, and the secondary clarifying agent is one or more of a 101 fruit juice clarifying agent, chitosan, a ZTC1+1 clarifying agent, a JH clarifying agent and gelatin;
(6) sterilizing the filtrate E under ultrahigh static pressure.
2. The infantile heat-clearing oral liquid of claim 1, wherein the sweetener is one or more of sucrose, high fructose syrup, xylitol, glycyrrhizin and stevioside; the essence is one or more of orange essence, strawberry essence, lemon essence, blueberry essence, raspberry essence, blackberry essence, waxberry essence, smoked plum essence and preserved plum essence.
3. The infantile heat-clearing oral liquid with fermented soybean and fructus forsythiae according to claim 2 is characterized in that the sweetening agent is stevioside.
4. The infantile heat-clearing oral liquid according to claim 2, wherein the essence is orange essence.
5. A preparation method of the children heat-clearing oral liquid prepared from fermented soybeans and fructus forsythiae, which is disclosed by claim 1, is characterized by comprising the following steps of:
(1) decocting fructus forsythiae, herba Menthae, herba Schizonepetae, and bupleuri radix in water, extracting volatile oil by steam distillation, mixing with 40-80% ethanol to obtain substance A, and collecting the water solution and the residue; in the step (1), the mass ratio of the total mass of the forsythia, the mint, the schizonepeta and the radix bupleuri to water is 1:4-6, the decoction is carried out for 2-4h, and the volume ratio of the volatile oil to 40-80% of ethanol is 1: 0.8-1.2;
(2) adding dextrin into water at 85-95 ℃ to prepare a dextrin water solution with the mass fraction of 55-65%, cooling to 40-50 ℃, carrying out ultrasonic treatment while stirring the dextrin water solution, adding 50-60% of a substance A, continuing ultrasonic treatment for 30-60min after the addition is finished, adding colloidal silicon dioxide SYLOID244FP, grinding, adding the rest substance A, grinding, drying, washing with absolute ethyl alcohol, and drying to obtain a substance B, wherein the mass-volume ratio of the dextrin to the volatile oil in the step (1) is 14-18:1 g/mL;
(3) decocting semen Sojae Preparatum, fructus Gardeniae preparata, radix et rhizoma Rhei, herba Artemisiae Annuae, radix Paeoniae Rubra, Arecae semen, cortex Magnolia officinalis, Scutellariae radix, rhizoma Pinelliae, Glycyrrhrizae radix and the residue in step (1) with water for 1-3 times, filtering, mixing the decoctions and the distilled water solution in step (1) to obtain solution C;
(4) concentrating the solution C to 55 deg.C relative density of 1.05-1.10, mixing with anhydrous ethanol to make ethanol content 60-70%, standing for 10-15 hr, filtering, recovering ethanol from filtrate, and concentrating to 55 deg.C relative density of 1.08-1.12 to obtain substance D;
(5) mixing substance D and substance B, adding water, filtering, mixing the filtrate with sweetener, antiseptic and essence, boiling for 0.5-1 hr, adding primary clarifier, standing, filtering, adding secondary clarifier, adding water, and filtering to obtain filtrate E; the primary clarifying agent is one or more of a 101 fruit juice clarifying agent, a ZTC1+1 clarifying agent, a JH clarifying agent and gelatin, and the secondary clarifying agent is one or more of a 101 fruit juice clarifying agent, chitosan, a ZTC1+1 clarifying agent, a JH clarifying agent and gelatin;
(6) sterilizing the filtrate E under ultrahigh static pressure.
6. The preparation method according to claim 5, wherein the fermented soybean, stir-fried gardenia, rhubarb, sweet wormwood herb, red peony root, areca nut, magnolia bark, scutellaria baicalensis, pinellia ternate and liquorice in the step (3) are decocted with water for 2 times, 7-9 times of water is added for 1-2 hours in the 1 st time, and 5-7 times of water is added for 0.5-1.5 hours in the 2 nd time.
7. The application of the infantile heat-clearing oral liquid prepared by any one of claims 1 to 4 or the preparation method of any one of claims 5 to 6 in preparing a medicament for treating infantile wind-heat type common cold.
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